This application is in the field of mass spectrometry and, more specifically, relates to ion guides to be used advantageously at interfaces between a high-pressure region and a low-pressure region. Mass spectrometers can be used to determine the molecular weight of gaseous compounds. The analysis of samples by mass spectrometry consists of three main steps, formation of gas phase ions from sample material, mass analysis of the ions to separate the ions from one another according to ion mass to charge ratio m/z, and detection of the ions. A variety of well-known means and methods exist in the field of mass spectrometry to perform each of these three functions. The particular combination of the means and methods used in a given mass spectrometer determine the characteristics of that instrument.
Before mass analysis can begin, gas phase ions must be formed from a sample material. If the sample material is sufficiently volatile, ions may be formed by electron ionization (EI) or chemical ionization (CI) of the gas phase sample molecules, for instance.
Atmospheric Pressure Ionization (API) includes a number of ion production means and methods. Typically, analyte ions are produced from liquid solution at atmospheric pressure. In one of the more widely used methods known as electrospray ionization (ESI), analyte is dissolved in a liquid solution and sprayed from a needle. The spray is induced by the application of a potential difference between the needle and a counter electrode. The spray results in the formation of fine, charged droplets of solution containing analyte molecules. In the gas phase, the solvent evaporates leaving behind charged gaseous analyte ions.
In addition to ESI, other ion production methods may be used at atmospheric or elevated pressure. For example, matrix-assisted laser desorption/ionization (MALDI) has been adapted to work at atmospheric pressure. The benefit of adapting ion sources in this manner generally is that the ion optics (that is, the electrode structure and operation) in the mass analyzer and mass spectral results obtained are largely independent of the ion production method used.
In hybrid analytical instruments, such as liquid chromatography/mass spectrometry (LC/MS) instruments, where two analytical techniques are coupled and the liquid output of one serves as the analytical input of the other, it is preferred to generate ions in an ion source which is maintained at (or near) atmospheric pressure.
Elevated pressure (that is, elevated relative to the pressure of the mass analyzer) and atmospheric pressure ion sources always have an ion production region wherein ions are produced, and an ion transfer region wherein ions are transferred through differential pumping stages into the mass analyzer. Generally, mass analyzers operate in a vacuum between 10−2 and 10−8 Pascal depending on the type of mass analyzer used. When using, for example, an ESI or elevated pressure MALDI source, ions are formed and initially reside in a high pressure region of “carrier” gas. In order for the gas phase ions to enter the mass analyzer, the ions must be separated from the carrier gas and transported through the single or multiple vacuum stages.
The use of multipole ion guides has been shown to be an effective means of transporting ions through a vacuum system, see for example U.S. Pat. No. 4,963,736 to Douglas et al. Under the generic name of “ion guide” different electrical devices are used, such as quadrupole, hexapole or octopole rod systems, but also stacked ring electrodes (see, for instance, U.S. Pat. No. 6,891,153 B2 to Bateman et al.). The function of the ion guides is to confine and transfer the ion beam throughout the intermediate vacuum stages via a radio frequency (RF) field generated by the guide itself. The normal operating pressure of such ion guides ranges from about 100 to 10,000 Pascal. A novel way of micro-engineering stacked ring ion guides has been presented recently by Syms et al. (U.S. Pat. No. 7,960,693 B2).
One of the principal differences between multipole rod ion guides and stacked ring electrode ion guides is the manner of electrical wiring, or in other words the electrical contacting. Rod ion guides conventionally comprise an even number of elongated pole rods arranged around a longitudinal axis under rotational symmetry. The wiring is (or in other words, the electrical contacts are arranged) normally such that two opposing rods receive the same phase of a radio frequency potential whereas other pairs of opposing rods receive different phases of the same RF potential. In other words, the pole rods receive different phases of an RF potential in a “cross-wise” manner.
On the other hand, stacked ring ion guides are wired such that, along the row of rings, adjacent rings receive alternating phases (normally, 180 degrees out of phase) of an RF potential. In other words, the stacked ring electrodes receive different phases of an RF potential in an “axially alternating” manner. As a result, stacked ring ion guides generally have a narrow range of effective geometries. That is, the thickness of the rings and the gap between the rings must be relatively small compared to the size of the inner aperture of the ring. Otherwise, ions may get trapped in pseudopotential “wells” in the ion guide and therefore not be efficiently transmitted.
Another means for guiding ions at “near atmospheric” pressures (that is, pressures between about 10 and 105 Pascal) is disclosed by Smith et al. (U.S. Pat. No. 6,107,628 A). One embodiment consists of a row of rings the inner apertures of which gradually decrease along the row. Thus the aggregate of the apertures form a “funnel” shape, otherwise known as an ion funnel. The ion funnel has an entry corresponding with the largest aperture, and an exit corresponding with the smallest aperture. The row of rings is wired in the axially alternating manner as mentioned before. Further, a direct current (DC) electrical gradient is created using a power supply and a resistor chain to supply the desired and sufficient voltage to each ring to create a driving force for ions to be transported through the funnel. Additional driving forces may be necessary with ion funnels since the pseudopotentials created therein, due to the tapering aperture of the rings, could otherwise be ion repulsive along the axis.
Generally, the ion funnel has the advantage, when properly operated, that it can efficiently transmit ions through a relatively high pressure region (that is, larger than about 10 Pascal) of a vacuum system, whereas multipole ion guides perform poorly at such pressures. However, the ion funnel generally performs poorly at lower pressures where multipole ion guides transmit ions efficiently.
FIG. 1 shows an exemplary mass spectrometer arrangement according to prior art. On the left it has an ion source with an ion source housing 6 which, in this case, is equipped with an electrospray capillary 4 protruding into the ion source housing 6 and being supplied with a sample solution by reservoir 2. Opposite to the spray capillary 4, the ion source housing 6 has a waste or exhaust port 8 through which superfluous solvent mist is removed. The ion source housing 6 is coupled to a mass spectrometer assembly having four differential pumping chambers 30, 32, 34 and 36. The pressure in these pumping chambers 30, 32, 34 and 36, by way of example, can amount to 300, 3, 0.03, and 3×10−4 Pascal, respectively. The pressures in the pumping stages 30, 32, 34 and 36 are set and maintained by vacuum pumps 31, 33, 35 and 37. The first vacuum chamber 30 has an inlet capillary 10 in an off-axis position which, on the ion source housing side, receives ions from the sample solution injected into the ion source housing 6. The off-axis position of inlet capillary 10 is useful as it prevents droplets from flying directly through the device to the ion detector 48.
The other side of the inlet capillary 10 is opposite a stacked ring ion funnel 16 as known, for example, from the aforementioned disclosure by Smith et al. The ion funnel 16 is connected to an RF+DC voltage generation network 12, 14 which supplies RF voltages to the individual rings with axially alternating phase so that pseudopotentials necessary for radial confinement can be created. The separate electrodes of the stacked ring ion funnel 16 can also be supplied with a DC potential gradient along the axis in order to provide additional driving force acting on the ions to drive them through the funnel 16. With the largest aperture ring electrode facing the outlet of the inlet capillary 10 and the smallest aperture ring electrode facing an insulated orifice plate 50 at the interface to the next differential pumping chamber 32, which allows the generation of a potential drop along the ion pathway, the stacked ring ion funnel 16 has a large acceptance profile for ions passing the inlet capillary 10 and, along its axis by means of its tapering aperture, promotes radial focusing so that, upon exiting the funnel 16, the outer dimension of the ion stream is small enough to pass the insulated orifice plate 50 without much ion loss.
The vacuum chambers 32, 34 downstream of the vacuum chamber 30 with the ion funnel 16 may then each have a quadrupole rod ion guide 42, 44 as known from the aforementioned disclosure of Douglas et al., for instance, as well as further insulated orifice plates 52 and 54 at the downstream interfaces, respectively. Due to the radial focusing of the ions in the ion funnel 16 the rod ion guides 42, 44 are well suited to transfer the ions further without significant ion loss. The last vacuum chamber 36 in this example then has a quadrupole rod mass filter 46 as is well known in the art. By applying appropriate RF and DC voltages to the pole rods of the mass filter 46 a window of mass to charge ratios m/z can be set, or a range of corresponding windows can be scanned through, to allow ions having the respective mass to charge ratio m/z to pass the mass filter 46 and reach the ion detector 48 where they can be measured as a function of the voltage conditions applied.
Recently, Kim et al. (U.S. Pat. No. 7,851,752 B2 which is incorporated by reference in its entirety in the present disclosure) proposed a new ion guide design which encompasses the features of a cross-wise wiring and an axially alternating wiring at the same time. The design includes segmenting each ring (or electrode) in a conventional stacked ring ion guide design into a number of electrically conductive regions separated from each other by insulating regions, and supplying the electrically conductive regions of each electrode, as known from multipole rod ion guides, in a cross-wise manner while also, as known from stacked ring ion guides, providing axially alternating phase differences between electrically conductive regions of adjacent electrodes in the row, which are aligned with each other. Thereby, in particular, the presence of undesired trapping pseudopotential wells between adjacent electrodes in the stack is supposed to be overcome. However, the assembly of Kim's ion guide turns out to be rather cumbersome as it is suggested to provide ring-shaped electrically insulating supports to which metal foils are bonded in the areas designated for the electrically conductive regions. All these electrically conductive regions then have to be wired according to the desired electrical circuitry. This procedure is rather time consuming as every single electrode in the stack has to be machined individually.
In view of the above a need exists to provide an ion guide that includes the favorable combined wiring in an axially alternating as well as a cross-wise manner while, in particular, being easier to fabricate and assemble.